The use of natural and synthetic bone grafting materials in reconstructive surgery has been well established. Autogenous bone is typically preferred for the repair of bony defects in a variety of dental and orthopedic clinical procedures. Although it is desirable to use autogenous bone for defect repair, it is often in limited supply and there are problems associated with the surgery to harvest these grafts. Allografts are a popular alternative to autografts for promoting osseous ingrowth. Although there is an abundance of these cadaver harvested grafts, allografts have their associated problems, including possible disease transmission, incomplete incorporation and lot to lot variability with respect to its capability to induce osseous in-growth. As a result, synthetic bone grafting materials have become popular for use in these types of procedures.
Many calcium phosphate based ceramics have been developed for use as bone grafting substitutes. Bioactive glasses and glass ceramics are examples of these synthetic bone grafting materials. Bioactive glasses and glass ceramics have been utilized as bone replacement materials in a variety of dental and orthopedic reconstructive surgical techniques. These glasses develop a strong bond with hard tissue due to a series of ion exchange reactions between the implant surface and body fluids that result in the formation of a biologically active calcium phosphate film at the implant tissue interface. See Hench et al, J. Biomed. Mater. Res., Vol. 5, pp. 117-141 (1971), and Hench et at, J. Biomed. Mater. Res., Vol. 7, pp. 25-42 (1973). Bioactive glasses also have been shown to form a firm bond with soft tissue. See Wilson, et al, J. Biomed. Mater. Res., Vol. 15, pp. 805-817 (1981); Wilson and Merwin, J. Biomed. Mater. Res.: Applied Biomaterials, Vol. 22, No. A2, pp. 159-177 (1988); and Wilson, Low et al, Biomaterials and Clinical Applications, Ed. By Pizzoferrato et al, Elsevier Science Publishers B. V., Amsterdam (1987).
Certain bioactive and biocompatible glasses and glass-ceramics, e.g., those described in U.S. Pat. Nos. 4,159,358; 4,234,972; 4,103,002; 4,189,325; 4,171,544; 4,775,646; 4,851,046,and 5,074,916 (all incorporated herein by reference), have been shown to develop a unique, strongly adherent, chemical bond with hard tissue (bone). This is a result of the formation of a biologically active calcium phosphate (hydroxycarbonate apatite) film generated in situ by ion-exchange reactions between the glass or glass-ceramic surface and body fluids. This influence results in a strong fixation of the glass or glass-ceramic to the bone surface.
The particulate form of bioactive glasses has been used in the repair of periodontal defects in humans for several years. The material is usually mixed with sterile saline, or the patient's own blood, which forms a coherent mass and remains workable for several minutes before placement in the defect site. Although this approach works well for smaller defect sites, there is the need for filling larger defects where it is desirable to have a more malleable material that can be easily shaped and placed into the defect site. Such a material should be sufficiently cohesive to prevent the problems of particle migration associated with some particulate grafting materials. This type of moldable grafting material can be used in a variety of reconstructive surgical procedures including to orthopedic, maxillofacial and dental applications.
Several approaches to defect repair in these procedures include the use of natural and synthetic constituents to achieve the desired osteoconductive and handling properties described above. These graft materials may be in the form of a paste or putty, which either retains its malleable characteristics after implantation, or hardens in situ, similar to a cement. An example of the use of calcium phosphate based cements as a bone filling material is described in U.S. Pat. No. 5,522,893. This patent describes a combination of tetracalcium phosphate and dicalcium phosphate salts that are mixed and react to harden and form a hydroxycarbonate (HCA) apatite after implantation. Although the HCA that forms effectively fills the defect site, the material is not osteoconductive. The material is relatively insoluble in water and non-absorbable, being only partially replaced by natural bone tissue.
U.S. Pat. No. 5,263,985 ("the '985 patent") describes an implantable material for promoting bone growth which has a microporous structure exhibiting an average pore size of at least 30 Angstroms. The porous biomaterial is capable of retaining macromolecules having a molecular weight of at least 15,000 and up to 500,000. The '985 patent further describes the use of dextran beads having controlled pore size to stimulate bone and tissue growth. However, only negatively charged beads displayed an osteoinductive effect.
Dextrans have been used as femoral plugs. See Rodriguez et al., Optimization of the mechanical properties of dextran-based femoral plugs, Congr. Int. Technol. Pharm., 05.sup.th 1989, 4, 376-90 which describes compressed dextran powders for use as femoral bone plugs tested for their resistance to disintegration and for their plasticity as a function of molecular weight (17,200 to 5-40 million). Preliminary in vivo results showed that the plugs were completely absorbed at the end of 2 to 20 days.
Dextrans have also been combined with hydroxyapatite. See Manufacture of artificial bones from powdery hydroxylapatite and dextran, Nagase, Japan Kokei Tokyo Koho JP 63-189,156 Aug. 4, 1988. Hydroxyapatite is not class A bioactive. This article describes artificial bones and prosthetics prepared by mixing hydroxyapatite and dextran with or without water or saline solution. Saline was added to sterilized dextran and mixed with hydroxylapatite powder. The resulting plastic paste was added to bone's missing parts.
In the past, other carriers such as polymethylmethacrylate, glycol dimethacrylate, and polylactic dimethacyrate have been used as carriers for bioactive implant materials. However, these materials are not resorbable or degrade very slowly and are typically associated with soft tissue infiltration.